Pregnant women living in poverty often experience chronic stress and consequently higher levels of stress hormones. In utero exposure to high levels of stress hormones can negatively affect the developing fetus and the infant's capacity for emotion and behavioral regulation. In this application we describe a developing program of research designed to reduce the negative impact of prenatal stress on infant health and development via nutritional supplementation of docosahexaenoic acid (DHA) during pregnancy. DHA is a long-chain polyunsaturated fatty acid member of the omega-3 fatty acid family. DHA is found in its highest concentrations in neural cell membranes, affecting receptor function, neurotransmitter uptake, and signal transmission. There is growing evidence that low levels of dietary DHA intake are associated with suboptimal response to stress and that DHA supplementation can modulate stress response. Aims: The goals of the proposed study are to test whether DHA supplementation during pregnancy is associated with 1) improved maternal health during pregnancy among African American women living in urban poverty; 2) improved infant birth and neurodevelopmental outcomes, and 3) whether the association between DHA supplementation during pregnancy and infant outcomes is partially mediated by reductions in maternal perceived stress and stress reactivity during pregnancy. Approach: One hundred sixty-two pregnant African American women living in urban poverty, who consume less than two servings of fish per week, will be randomly assigned to receive 450 mg/daily of DHA or placebo beginning at 9-12 weeks of gestation through the end of pregnancy. Perceived stress, stressful life events, anxiety, and depression, inflammatory markers, DHA levels and response to a laboratory stressor will be assessed at baseline and at 24, 30, and 36 weeks of pregnancy. Neonatal outcomes (e.g., gestational age, birth weight, delivery complications) will be collected from medical records, and infant neurodevelopmental outcomes and stress reactivity will be assessed at 1, 4 and 9 months of age. Investigators: This application builds on a recently completed NICHD/NIMH funded R21 (PI: Keenan), which yielded preliminary evidence that DHA supplementation during pregnancy reduces perceived stress and cortisol response to stress in pregnant African American women living in low-income, urban environments. Drs. Keenan and Hipwell and Ms. Wroblewksi were investigators on the R21 and will continue to work together on the proposed study. Dr. Della Torre is an Assistant Professor of Obstetrics at the University of Chicago, who specializes in providing clinical services to African American women living in the south side of Chicago. Innovation: This will be the first large randomized controlled study of the effect of DHA supplementation in pregnant African American women living in urban poverty on maternal and infant health and stress response. Impact: If DHA supplementation is associated with reductions in perceived stress, more modulated maternal cortisol response to stress, and more optimal emotional and behavioral regulation in the infant, even within the context urban poverty, then a comprehensive program of research on the mechanisms by which these associations evolve can be launched and broad-based prevention interventions that target maternal and child in vulnerable populations can be implemented, potentially leading to reductions health disparities in the U.S.